The present invention relates to systems and methods for determining a minimum effective dose of an inhaled drug for an individual patient at a given time and, more particularly, to systems and methods for computing, and optionally delivering a minimum effective dose of an inhaled medication based upon results of a single measurement of a pulmonary performance indicator immediately prior to inhalation of the medication. The invention is expected to find special utility in care and treatment of chronic asthma patients.
Metered dose inhalers are widely employed to treat respiratory conditions. Typically, a metered dose inhaler delivers a predetermined dose of an aerosolized drug with each actuation of a delivery mechanism. The most common configuration employs pressurized gas to move a drug through a narrow opening where the drug is aerosolized. The device is typically positioned in the mouth or nostril(s) of a patient so that the aerosolized drug is delivered to the appropriate region of the airway Metered dose inhalers share a common inherent disadvantage. Although delivery is exact, dosage is formulated based upon research on large populations of patients. This inherent disadvantage creates two problems. The first problem is that patients may take more medication than they actually require. The second problem is that some patients may require more medication than recommended on some occasions.
The number of patients using metered dose inhalers on a routine basis is quite large. For example, asthma affects approximately 10–15% of children and 5–10% of adults. The American Thoracic Society, the American Lung Association and the European Respiratory Society (Kamada et al. Issues in the use of inhaled glucocorticoids. Am J Respir Crit Care Med 1996;153:1739–48) recommend on going treatment for 80% of these asthma patients with inhaled corticosteroids or glucocorticoids (IGC). The device of choice for administration of these inhaled corticosteroids is a metered dose inhaler.
It is well established that IGC are effective in the treatment of asthma. (Kamada et al. Issues in the use of inhaled glucocorticoids. Am J Respir Crit Care Med 1996;153:1739–48). However, IGC have the potential to cause severe adverse systemic effects. For example chronic long term use of IGC has been reported to cause adrenal suppression, osteoporosis and growth suppression in children (Doull et al. Growth of asthmatic children on inhaled corticosteroids (abstract). Am Rev Respir Dis 1993;147:A265, Littlewood J M, Johnson A W, Edwards P A, et al. Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate. Lancet 1988;i:115–6, Wales J K H, Barnes N D, Swift P G F. Growth retardation in children on steroids in asthma. Lancet 1991;338:1535–6, Wolthers O D, Pederson S. Controlled study of linear growth in asthmatic children during treatment with inhaled corticosteroids. Pediatrics 1992;89:839–42, Wolthers O D, Pederson S. Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate. Arch Dis Child 1993;68:673–6, Prifitsk K, Milner A D, Conway E, et al. Adrenal function in asthma. Arch Dis Child 1990;65:838–40). The danger of these adverse effects increases with the amount of IGC consumed (Dahl R, Lundback B, Malo J-L. A dose ranging study of fluticasone propionate in adult patients with moderate asthma. Chest 1993;104:1352–8).
Studies indicate that dose-dependent suppression of the hypothalamic-pituitary-adrenal axis (HPAA) occurs in both healthy volunteers and in asthmatics (Nikolaizik et al. Nocturnal cortisol secretion in healthy adults before and after inhalation of budesonide. Am J Respir Crit Care Med 1996;153:97–101, Donnelly et al. Effects of budesonide and fluticasone on 24-hour plasma cortisol. Am J Respir Crit Care Med 1997;156:1746–51). This suppression occurs even following a single dose inhalation of IGC. Systemic bioavailability of IGC is a function of absorption of the drug across the lung vascular bed. Lung deposition and systemic bioavailability are altered airway diameter in patients with asthma. Further, the degree of narrowing varies widely, both among patients within the population and as a function of time for each individual patient (Weiner et al. Characteristics of asthma in the elderly. Eur Respir J 1998;12 (3):564–8).
Thus, the inability of standard IGC therapy regimens employing fixed dose metered dose inhalers to customize the dose to the requirements of an individual patient at a specific time poses a significant risk to many asthma patients.
Although current guidelines on asthma treatment recommend the administration of the lowest dose of IGC compatible with asthma control, computation of this dose is most often based upon analysis of responses of a large population of patients. In cases where individual patients have their pulmonary function quantitatively analyzed, such analyses are generally performed periodically, not daily or prior to each inhalation of IGC.
Further, it is widely believed by clinicians that improved asthma control can be achieved by increasing the dose of IGCs. Thus, there is a tendency to empirically determine how much IGC is required to provide relief from an acute asthma attack and advise patients to continue to apply this high dosage. Such practice ignores the idea that the dose of IGC should be reduced as soon as control is achieved. This is because the tendency for each unit of IGC delivered to the airway to exert a systemic effect increases as the patients condition stabilizes or improves.
U.S. Pat. No. 5,724,986 issued to Jones Jr. et al teaches a casing and spirometer for a metered dose inhaler. Jones Jr. teaches measurement of a pulmonary parameter such as peak expiratory flow (PEF). However, Jones Jr. fails to teach use of this measurement to compute a minimum effective dose. Instead, Jones Jr. teaches determination of an optimum time to release medication from a metered dose inhaler. According to the teachings of Jones Jr., the optimum time is chosen to insure maximum delivery of the inhaled medication to the lungs (as opposed to the upper airway) regardless of the physiologic condition of the patient. Thus the teachings of Jones Jr. increase the amount of medication delivered systemically and increase the risks associated with systemic administration of medication.
U.S. Pat. No. 5,826,570 issued to Goodman et al. teaches delivery of aerosol medications for inspiration. Goodman, like Jones Jr., teaches determination of an optimum time to release medication from a metered dose inhaler. Goodman teaches choosing a desired location for deposition of the inhaled medication. Like Jones Jr., Goodman teaches maximization of the respirable fraction of the aerosolized medication. Thus, like Jones Jr., Goodman teaches increasing the amount of medication delivered systemically thereby increasing the risks associated with systemic administration of medication. Further, Goodman teaches calculations based upon repeated measurements. This is an inherent disadvantage because it increases the amount of time required for a patient to measure pulmonary function prior to beginning treatment.
There is thus a need for, and it would be highly advantageous to have, systems and methods for determining a minimum effective dose of an inhaled drug for an individual patient at a given time devoid of the above limitations.